The major aim of this research is to broaden our understanding of how the adult pattern of precise and orderly connections in the mammalian CNS is achieved during development. Order in the adult CNS is exemplified in the visual system and the present research is centered around the question, "How are segregation of eye input and topographic order established during the prenatal development of the cat's visual system?" To answer this question a number of different aspects are being studied. One concerns the normal time course of development of connections between retina, lateral geniculate nucleus (LGN) and visual cortex: when do these connections form and when are the adult patterns of topography and segregation of eye input attained? Segregation is being studied in detail at the level of the LGN: what roles are played by synaptogenesis and the formation of functional synaptic connections in attaining the segregated state? Another aspect concerns the prenatal development of visual connections in the Siamese cat. In these animals the topographic map of the visual field contained within the LGN and visual cortex has been systematically altered due to a genetic mutation. The developmental events associated with this alteration are under study, with the expectation that knowledge of these events will broaden the understanding of both abnormal and normal development of connections in the mammalian CNS. A variety of modern surgical and neuroanatomical methods are being used. Development of connections between regina, LGN and cortex is being studied by means of the anterograde transport of horseradish peroxidase (HRP) or 3H-amino acids injected intraocularly into fetuses of known gestational age, followed by histochemistry or autoradiography. Development of topographic order will be examined by using retrograde transport of HRP or fluorescent dyes injected into LGN and cortical plate. An electron microscopic study of synaptogenesis has been initiated, and the presence of functional connections is being assessed by the newly developed method of in vitro fetal electrophysiology.